We propose the continued development of a new biochemical measurement technique which combines the specificity of enzymes with the high sensitivity and rapid time resolution of mass-spectroscopy. The basic concept is the enzyme-catalyzed conversion of non-volatile substrate molecules (e.g. urea) to volatile, membrane-permeable molecules (e.g. CO2) by enzymes (e.g. urease) immobilized on a thin synthetic membrane, the opposite side of which is exposed to the vacuum of a relatively inexpensive mass-spectrometer. Depending on the particular configuration, most or all of the volatile product permeates the synthetic membrane and evaporates into the vacuum region. By the use of techniques developed and under development for molecule microscopy, a fraction 10 to the minus of the 4th power or more of the individual volatile product molecules can be counted, so that detection sensitivities on the order of 10 to the minus of the 20th power moles with rapid time resolution (on the order of 10 seconds) should ultimately be attained. Coenzymes, inhibitors, and volatile substrates can also be measured. For example, in a preliminary study, the conversion of acetaldehyde to the volatile ethanol (catalyzed by alcohol dehydrogenase) was used to measure the coenzyme NADH (nicotinamide adenine dinucleotide). Measurements of urea by using immobilized urease and CO2 as the volatile have also been made. A large number of enzyme reactions appear suitable for this technique. In one variation of this instrument, we expect to be able to assay for suitable enzymes with even greater sensitivity. The technique proposed should also be directly applicable without significant dilution to very small samples (e.g. 10 to the minus of 8th power ml) in which the substrate, coenzyme, inhibitor, or enzyme concentration is fairly high (e.g. 10 to the minus 4th power M). Preliminary work (Appendix A) using a highly non-optimal apparatus supports our expectations. Furthermore this new technique can be combined with molecule microscopy (Appendix C) to provide a means for spatially mapping enzyme activity in tissue samples in real time. No stain is used. A very thin (approximately 300 A) synthetic membrane separates the sample from the vacuum system of a molecule microscope. When substrates, etc. are provided in the bathing medium, the spatial distribution of enzymes in (Text Truncated - Exceeds Capacity)